: The foundation of this proposal is a well-established and highly successful preclinical research platform within Cleveland Clinic's Lerner Research Institute (LRI), which investigates animal models of clinically relevant diseases. The existing capabilities of this platform include 1) generation of rodent and other larger animal models of human disease, 2) characterization of pathology and physiology in these models, 3) development of novel therapeutics to be tested in these models, and (4) state-of-the-art technologies and instrumentation. The success of this platform is due largely to LRI's well-established Core Facility infrastructure that provides state-of-the-art instrumentation and novel technologies to all Cleveland Clinic investigators and collaborators. Currently, several Imaging Core facilities are available to investigators, including anatomic imaging (micro-MRI, micro-CT, and ultrasound) and optical imaging (bioluminescence, fluorescence, and microscopy). However, there is a critical missing piece to the Imaging Core infrastructure here: the capability of in vivo molecular imaging of radiotracers. High-resolution PET is not available onsite to Cleveland Clinic investigators, yet many NIH-funded and other investigators have been identified who would greatly benefit from on-site access to micro-PET, in addition to those already using micro-CT. Thus in this application, funds are requested towards the acquisition of a Mediso nanoScan PET/CT 122S instrument, which will fill the missing piece of our imaging platform. This instrument produces high-resolution in vivo CT, PET, or combined PET/CT images. If awarded, it will be installed adjacent to an existing micro- MRI scanner to allow for sequential PET/CT/MRI imaging. The new instrument will greatly benefit many NIH-funded and other research projects. As the first high-resolution PET scanner at Cleveland Clinic, it will provide local access to a valuable technique for research laboratories. It also will replace an aging micro-CT scanner and will provide considerable improvements in image quality and throughput. A key feature of the nanoScan PET/CT is that its bore diameter is considerably larger than typical small animal scanners, which will allow animals or specimens larger than mice or rats to be scanned with high resolution. The larger bore diameter will benefit several projects and will introduce a new regional capability to Cleveland-area investigators. The nanoScan PET/CT will fill a significant need and will complement other core imaging facilities at our institution. The availability of noninvasive in vivo molecular imaging will enhance research projects by visualizing and quantifying biochemical processes at the cellular level in animal models of human diseases. This instrument will support ongoing and future translational research at Cleveland Clinic and will contribute to new discoveries and clinical applications.